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- Title
Metabolic effects of muraglitazar in type 2 diabetic subjects.
- Authors
Fernandez, M.; Gastaldelli, A.; Triplitt, C.; Hardies, J.; Casolaro, A.; Petz, R.; Tantiwong, P.; Musi, N.; Cersosimo, E.; Ferrannini, E.; DeFronzo, R. A.
- Abstract
Aim: To assess the effect of muraglitazar, a dual peroxisome proliferator-activated receptor (PPAR) γ- α agonist, versus placebo on metabolic parameters and body composition in subjects with type 2 diabetes mellitus (T2DM). Methods: Twenty-seven T2DM subjects received oral glucose tolerance test (OGTT), euglycaemic insulin clamp with deuterated glucose, measurement of total body fat (DEXA), quantitation of muscle/liver (MRS) and abdominal subcutaneous and visceral (MRI) fat, and then were randomized to receive, in addition to diet, muraglitazar (MURA), 5 mg/day, or placebo (PLAC) for 4 months. Results: HbA1cc decreased similarly (2.1%) during both MURA and PLAC treatments despite significant weight gain with MURA (+2.5 kg) and weight loss with PLAC (−0.7 kg). Plasma triglyceride, LDL cholesterol, free fatty acid (FFA), hsCRP levels all decreased with MURA while plasma adiponectin and HDL cholesterol increased (p < 0.05-0.001). Total body (muscle), hepatic and adipose tissue sensitivity to insulin and β cell function all improved with MURA (p < 0.05-0.01). Intramyocellular, hepatic and abdominal visceral fat content decreased, while total body and subcutaneous abdominal fat increased with MURA (p < 0.05-0.01). Conclusions: Muraglitazar (i) improves glycaemic control by enhancing insulin sensitivity and β cell function in T2DM subjects, (ii) improves multiple cardiovascular risk factors, (iii) reduces muscle, visceral and hepatic fat content in T2DM subjects. Despite similar reduction in A1c with PLAC/diet, insulin sensitivity and β cell function did not improve significantly.
- Subjects
TYPE 2 diabetes; METABOLIC disorders; INSULIN resistance; GLUCOSE tolerance tests; FAT cells; DRUG development
- Publication
Diabetes, Obesity & Metabolism, 2011, Vol 13, Issue 10, p893
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2011.01429.x